Precision in treatment evaluation: importance of minimal clinically important differences (MCIDs) of outcome measures for autoimmune blistering diseases

Autoimmune blistering diseases (AIBDs) comprise a group of rare conditions marked by autoantibodies that specifically target intercellular adhesion molecules. Despite the progress made in comprehending the disease and the increasing number of treatment options available, there is still no definitive cure for AIBDs such as pemphigus, and it continues to have a devastating impact on those affected. The challenges in achieving new approved therapies for AIBDs are complex and multifaceted. One significant obstacle was the prior lack of validated and standardized outcome measures, which are crucial for ensuring precise comparisons between new and traditional therapies. This gap in knowledge has prompted the development of minimal clinically important differences (MCIDs), which enable efficient and reliable comparison of therapeutic outcomes between trials. MCID is defined as the minimum difference in an outcome measure that indicates a clinically significant improvement/deterioration in disease severity. Additionally, MCIDs provide a patient-centered approach to evaluating treatment efficacy, by considering whether patients experience a subjective improvement in their symptoms. Therefore, this literature review will examine the derivation and significance of MCIDs for various scoring systems in AIBDs

The development of an Excel® spreadsheet to document disease activity in autoimmune bullous disease

We have developed a specialised Excel® spreadsheet which records a panel of clinical variables for patients presenting to specialised bullous clinics at our institution. The spreadsheet incorporates scores for the two disease specific instruments for autoimmune bullous disease; the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and the Pemphigus Disease Area Index (PDAI), as well as medication doses, and quality of life (QOL) scores. The spreadsheet has automated arithmetic functions for tallying scores, explanatory pop-ups and restrictions on data values to prevent the inadvertent input of invalid data. The major strength of the spreadsheet is that using the graph function, one can instantly appreciated how the disease trajectory of a patient has evolved across a range of parameters (such as disease activity, QOL and the need for immunosuppression) through the visual depiction of their clinical course. The spreadsheet built by our group is practical for routine clinical use and is a useful tool for longitudinal monitoring of disease activity in bullous patients.</p

Low levels of ATM in breast cancer patients with clinical radiosensitivity

BACKGROUND AND PURPOSE Adjuvant radiotherapy for cancer can result in severe adverse side effects for normal tissues. In this respect, individuals with anomalies of the ATM (ataxia telangiectasia) protein/gene are of particular interest as they may be at risk of both breast cancer and clinical radiosensitivity. The association of specific ATM gene mutations with these pathologies has been well documented, however, there is uncertainty regarding pathological thresholds for the ATM protein. RESULTS Semi-quantitative immuno-blotting provided a reliable and reproducible method to compare levels of the ATM protein for a rare cohort of 20 cancer patients selected on the basis of their severe adverse normal tissue reactions to radiotherapy. We found that 4/12 (33%) of the breast cancer patients with severe adverse normal tissue reactions following radiotherapy had ATM protein levels < 55% compared to the mean for non-reactor controls. CONCLUSIONS ATM mutations are generally considered low risk alleles for breast cancer and clinical radiosensitivity. From results reported here we propose a tentative ATM protein threshold of ~55% for high-risk of clinical radiosensitivity for breast cancer patients.The authors acknowledge grant support from the Royal Australian and New Zealand College of Radiologists

Hair Loss in Autoimmune Cutaneous Bullous Disorders

The expression of the basement membrane zone (BMZ) components in the anagen hair follicles of the human scalp is similar to that of interfollicular epidermis. Expression of the BMZ components varies according to the different follicular portions. Blistering of the scalp, involving lamina lucida and below, usually leads to scarring alopecia secondary to the inflammatory process in the interfollicular epidermis and in the upper portion of the hair follicle. This article discusses the presence of alopecia in the most common acquired forms of bullous disorders

Alopecia in epidermolysis bullosa

Hair abnormalities observed in epidermolysis bullosa (EB) are of variable severity and include mild hair shaft abnormalities, patchy cicatricial alopecia, cicatricial alopecia with a male pattern distribution, and alopecia universalis. Alopecia is usually secondary to blistering, and scalp areas more exposed to friction, such as the occipital area, are involved more frequently. This article reviews the hair abnormalities reported in the different subtypes of EB

Nail Involvement in Autoimmune Bullous Disorders

Autoimmune bullous disorders frequently cause nail abnormalities, particularly paronychia and onychomadesis. In pemphigus vulgaris (PV) nail abnormalities can even precede skin findings. Nail lesions often relapse just before generalized disease exacerbation or recurrence. Severe nail changes are often associated with extensive and severe disease. Fingernails are more commonly affected. A report in the literature associates hemorrhagic nail abnormalities with poor prognosis in patients with PV. Nail scarring and pterygium are a rare complication of bullous pemphigoid. Nail loss has been occasionally reported in epidermolysis bullosa acquisita

Autoimmune Blistering Diseases in the Elderly: Clinical Presentations and Management.

Elderly patients are more susceptible to the development of autoimmune blistering disorders such as bullous pemphigoid, mucous membrane pemphigoid, epidermolysis bullosa acquisita, and paraneoplastic pemphigus. This article focuses on the clinical aspects of the aforementioned autoimmune blistering diseases and highlights the important factors involved in treating elderly patients. It is essential for clinicians to offer individualized treatment plans for these patients to optimize outcomes, as elderly patients often have multiple co-morbidities, polypharmacy, and suboptimal socioeconomic status that can adversely influence adequate compliance

Nail involvement in epidermolysis bullosa

Nail abnormalities are a common feature in most subtypes of epidermolysis bullosa (EB), and they recently have been included among the criteria for scoring EB severity. Trauma undoubtedly contributes to the development of nail dystrophy, and for this reason the great toenails often are affected more severely. The nail abnormalities may be the first or the only symptom of EB. Nail abnormalities observed in EB are not specific or pathognomonic, as they result from nail bed and matrix scarring. The spectrum of clinical severity is large, and nail abnormalities may cause severe disability or just be a mild cosmetic problem. This article reviews the nail abnormalities observed in EB

Table_1_Precision in treatment evaluation: importance of minimal clinically important differences (MCIDs) of outcome measures for autoimmune blistering diseases.docx

Autoimmune blistering diseases (AIBDs) comprise a group of rare conditions marked by autoantibodies that specifically target intercellular adhesion molecules. Despite the progress made in comprehending the disease and the increasing number of treatment options available, there is still no definitive cure for AIBDs such as pemphigus, and it continues to have a devastating impact on those affected. The challenges in achieving new approved therapies for AIBDs are complex and multifaceted. One significant obstacle was the prior lack of validated and standardized outcome measures, which are crucial for ensuring precise comparisons between new and traditional therapies. This gap in knowledge has prompted the development of minimal clinically important differences (MCIDs), which enable efficient and reliable comparison of therapeutic outcomes between trials. MCID is defined as the minimum difference in an outcome measure that indicates a clinically significant improvement/deterioration in disease severity. Additionally, MCIDs provide a patient-centered approach to evaluating treatment efficacy, by considering whether patients experience a subjective improvement in their symptoms. Therefore, this literature review will examine the derivation and significance of MCIDs for various scoring systems in AIBDs.</p

Evidence-based management of bullous pemphigoid

Bullous pemphigoid (BP) is the most common autoimmune subepidermal bullous disease typically affecting the elderly. Although different therapeutic regimens have been proposed, a review of the evidence is needed to aid clinicians in their decision making and management. Systemic therapies such as corticosteroids and adjuvants are effective in BP but are plagued with adverse effects, and potent topical steroids are an alternative treatment. This article reviews the evidence supporting different therapeutic options in the management of BP